Funding

Self-funded

Project code

PHBM5351024

Department

School of Medicine, Pharmacy and Biomedical Sciences

Start dates

October, February and April

Application deadline

Applications accepted all year round

Applications are invited for a self-funded, 3 year full-time or 6 year part-time PhD project.

The PhD will be based in the School of of Pharmacy and Biomedical Sciences and be jointly supervised by Dr Bennett Au and Dr Roja Hadianamrei.

 

The work on this project will:

  • Formulate novel lipid nanoparticles (LNPs) for effective mRNA encapsulation and delivery to the central nervous system and peripheral nervous system using a microfluidic approach.
  • Assess the extent of axon regeneration and functional recovery in mice treated with LNPs in various mouse models of nervous system injuries
  • Provide the candidate an opportunity to develop a wide variety of cutting-edge research techniques including nanotechnology, molecular biology, animal handling, fluorescence microscopy, UV and fluorescence spectroscopy, dynamic light scattering (DLS), electrophysiology, bioinformatics, and so forth.
  • Offer an excellent opportunity to work with interdisciplinary researchers worldwide including world-leading collaborators in the United Kingdom, Hong Kong, United States, and China.

Severe injuries to the nervous system usually result in life-long disabilities which largely affect the quality of life of the survivors. To have clinically meaningful functional recovery after nervous system injuries, the injured neurons need to regrow their axons and re-connect to their original targets for functional recovery. However, for some unknown reasons, the mature neurons lost their ability to regenerate their axons and thus patients usually showed limited functional improvement even after immediate surgical repairs and constant rehabilitation. Therefore, there is an urgent need to develop novel therapeutic interventions to address this unmet medical need. 

Previous studies from us and others have demonstrated that overexpression of key genes involved in axonal outgrowth, or silencing intrinsic growth barriers in injured neurons can induce robust axon regeneration leading to partial or even full functional recovery after injuries. While most of the studies highlighted the strong neuronal tropism and high transduction efficiency in some serotypes of adeno-associated viruses (AAV), the high cost of mass production of AAVs makes the viral-based gene therapy highly unaffordable to patients with limited financial support from the government or charity. To address this issue, the current project aims to develop a cost-effective, non-viral gene delivery system to effectively and stably overexpress or silence our gene-of-interest in injured neurons. The candidate will formulate lipid nanoparticles (LNPs) loaded with the mRNA of our targeted genes, and functionally characterize the efficacy of these mRNA-loaded LNPs in promoting axon regeneration and functional recovery after various forms of nervous system injuries, including but not limited to peripheral nerve injury, optic nerve injury, spinal cord injury and ischemic strokes. The candidate will utilize a multidisciplinary approach spanning cell biology (primary cell cultures, transfection and gene silencing), molecular biology (molecular cloning, qPCR and Western blot), microscopy (confocal/fluorescence/super-resolution microscopy and live-cell imaging), animal behavioural assessments, electrophysiology, optogenetics, and system biology (RNA-seq, bioinformatics and network analysis), to understand the molecular mechanisms underlying the promoting effects of the mRNA-LNP treatment. Ultimately, we believe this project will provide a novel therapeutic option to promote functional recovery in patients with nervous system injuries in the near future. 

 

 

Fees and funding

Visit the research subject area page for fees and funding information for this project.

Funding availability: Self-funded PhD students only. 

PhD full-time and part-time courses are eligible for the UK Government Doctoral Loan (UK and EU students only – eligibility criteria apply).

Bench fees

Some PhD projects may include additional fees – known as bench fees – for equipment and other consumables, and these will be added to your standard tuition fee. 

Entry Requirements

You'll need a good first degree from an internationally recognised university (minimum upper second class or equivalent, depending on your chosen course) or a Master’s degree in Biomedical or Biological Sciences or a related area. In exceptional cases, we may consider equivalent professional experience and/or Qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

  • Highly motivated with strong enthusiasm for multidisciplinary research.
  • Prior knowledge of neuroscience and/or nanomedicine is desirable but not essential.
  • Strong background in cell biology and molecular biology is highly desirable.
  • Experience in formulation and characterization of nanoparticulate drug/gene delivery systems is desirable.
  • Prior experience in animal handling and in vivo experiments is an advantage.

How to apply

We strongly encourage you to contact Dr. Bennett Au (bennett.au@port.ac.uk) or Dr. Roja Hadianamrei (roja.hadianamrei@port.ac.uk) to discuss your research interest before you apply, quoting the project code.

When you are ready to apply, please follow the 'Apply now' link on the Pharmacy, Pharmacology and Biomedical Sciences PhD subject area page and select the link for the relevant intake. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV. Our ‘How to Apply’ page offers further guidance on the PhD application process. 

When applying please quote project code:PHBM5351024